Wiz binds active promoters and CTCF-binding sites and is required for normal behaviour in the mouse
We previously identified Wiz in a mouse screen for epigenetic modifiers. Due to its known association with G9a/GLP, Wiz is generally considered a transcriptional repressor. Here, we provide evidence that it may also function as a transcriptional activator. Wiz levels are high in the brain, but its f...
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eLife Sciences Publications Ltd
2016-07-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/15082 |
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doaj-91bbae90d51a4662991b3158923111292021-05-05T00:28:43ZengeLife Sciences Publications LtdeLife2050-084X2016-07-01510.7554/eLife.15082Wiz binds active promoters and CTCF-binding sites and is required for normal behaviour in the mouseLuke Isbel0https://orcid.org/0000-0002-5270-4347Lexie Prokopuk1Haoyu Wu2Lucia Daxinger3Harald Oey4Alex Spurling5https://orcid.org/0000-0002-4368-6191Adam J Lawther6Matthew W Hale7Emma Whitelaw8https://orcid.org/0000-0002-2320-2903Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, Melbourne, AustraliaDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, Melbourne, AustraliaDepartment of Human Genetics, Leiden University Medical Centre, Leiden, The NetherlandsDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, Melbourne, Australia; Department of Human Genetics, Leiden University Medical Centre, Leiden, The NetherlandsDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, Melbourne, AustraliaDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, Melbourne, AustraliaDepartment of Psychology and Counselling, La Trobe University, Melbourne, Australia; School of Psychology and Public Health, La Trobe University, Melbourne, AustraliaDepartment of Psychology and Counselling, La Trobe University, Melbourne, Australia; School of Psychology and Public Health, La Trobe University, Melbourne, AustraliaDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, Melbourne, AustraliaWe previously identified Wiz in a mouse screen for epigenetic modifiers. Due to its known association with G9a/GLP, Wiz is generally considered a transcriptional repressor. Here, we provide evidence that it may also function as a transcriptional activator. Wiz levels are high in the brain, but its function and direct targets are unknown. ChIP-seq was performed in adult cerebellum and Wiz peaks were found at promoters and transcription factor CTCF binding sites. RNA-seq in Wiz mutant mice identified genes differentially regulated in adult cerebellum and embryonic brain. In embryonic brain most decreased in expression and included clustered protocadherin genes. These also decreased in adult cerebellum and showed strong Wiz ChIP-seq enrichment. Because a precise pattern of protocadherin gene expression is required for neuronal development, behavioural tests were carried out on mutant mice, revealing an anxiety-like phenotype. This is the first evidence of a role for Wiz in neural function.https://elifesciences.org/articles/15082epigeneticsmommewidely interspaced zinc finger motifs |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Luke Isbel Lexie Prokopuk Haoyu Wu Lucia Daxinger Harald Oey Alex Spurling Adam J Lawther Matthew W Hale Emma Whitelaw |
| spellingShingle |
Luke Isbel Lexie Prokopuk Haoyu Wu Lucia Daxinger Harald Oey Alex Spurling Adam J Lawther Matthew W Hale Emma Whitelaw Wiz binds active promoters and CTCF-binding sites and is required for normal behaviour in the mouse eLife epigenetics momme widely interspaced zinc finger motifs |
| author_facet |
Luke Isbel Lexie Prokopuk Haoyu Wu Lucia Daxinger Harald Oey Alex Spurling Adam J Lawther Matthew W Hale Emma Whitelaw |
| author_sort |
Luke Isbel |
| title |
Wiz binds active promoters and CTCF-binding sites and is required for normal behaviour in the mouse |
| title_short |
Wiz binds active promoters and CTCF-binding sites and is required for normal behaviour in the mouse |
| title_full |
Wiz binds active promoters and CTCF-binding sites and is required for normal behaviour in the mouse |
| title_fullStr |
Wiz binds active promoters and CTCF-binding sites and is required for normal behaviour in the mouse |
| title_full_unstemmed |
Wiz binds active promoters and CTCF-binding sites and is required for normal behaviour in the mouse |
| title_sort |
wiz binds active promoters and ctcf-binding sites and is required for normal behaviour in the mouse |
| publisher |
eLife Sciences Publications Ltd |
| series |
eLife |
| issn |
2050-084X |
| publishDate |
2016-07-01 |
| description |
We previously identified Wiz in a mouse screen for epigenetic modifiers. Due to its known association with G9a/GLP, Wiz is generally considered a transcriptional repressor. Here, we provide evidence that it may also function as a transcriptional activator. Wiz levels are high in the brain, but its function and direct targets are unknown. ChIP-seq was performed in adult cerebellum and Wiz peaks were found at promoters and transcription factor CTCF binding sites. RNA-seq in Wiz mutant mice identified genes differentially regulated in adult cerebellum and embryonic brain. In embryonic brain most decreased in expression and included clustered protocadherin genes. These also decreased in adult cerebellum and showed strong Wiz ChIP-seq enrichment. Because a precise pattern of protocadherin gene expression is required for neuronal development, behavioural tests were carried out on mutant mice, revealing an anxiety-like phenotype. This is the first evidence of a role for Wiz in neural function. |
| topic |
epigenetics momme widely interspaced zinc finger motifs |
| url |
https://elifesciences.org/articles/15082 |
| work_keys_str_mv |
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